I quote this fascinating bit of neuro-transmitter research from some 
French journal, abstract on PubMed. It struck me because our health 
board prescribing advisers have tried to sink escitalopram, even going 
so far as the pre-emptive strike of directing us to prescribe it 
generically even though there won't be a generic along for a few years. 
I have heard our advisers talking at depression meetings for GPs and I 
am not impressed with their knowledge or their experience of 
psycho-active drugs. I wonder what they'll make of the S and R enantiomers??

Declan

<<<1: Encephale. 2007 Mar-Apr;33(2):179-87.Click here to read Links
     [Escitalopram and citalopram: the unexpected role of the R-enantiomer]
     [Article in French]

     Jacquot C, David DJ, Gardier AM, Sánchez C.

     Fac Pharmacie, EA Serotonine et Neuropharmacologie, Univ. 
Paris-Sud, Rue Jean-Baptiste Clément, F-92296 Châtenay Malabry cedex, 
France.

     Citalopram, a selective serotonin reuptake inhibitor, is composed 
of 2 enantiomers, R-citalopram and S-citalopram, 2 different 
non-superimposable mirror image forms of the same molecule. Separating 
these 2 enantiomers has enabled studying their individual properties. 
Citalopram's pharmacologic activity is centered on the S enantiomer's 
high affinity for the serotonin transporter which is twice as high as 
citalopram's and 30 to 40 times higher than R-citalopram. This leads to 
an inhibition of serotonin reuptake two times higher for escitalopram 
compared with citalopram and confirms that citalopram's pharmacologic 
activity is due to the S-enantiomer. Contrary to what might be expected, 
the effect of escitalopram (DCI of S-citalopram) is not superimposable 
on an equivalent dose of citalopram but is superior. Several hypotheses 
could explain this superiority. First, conversions of the S-enantiomer 
into the R-enantiomer may occur, but there is no reason why this 
phenomenon would happen more when both enantiomers are present than when 
escitalopram is alone. Furthermore, pharmacokinetic studies have shown 
that S or R configurations are stable in vivo. Second, a particular 
action of R-citalopram may influence the S-enantiomer's kinetic from 
intestinal absorption to blood-brain barrier. But concentrations of both 
enantiomers in the frontal cortex are the same. Therefore, R-citalopram 
does not interfere with escitalopram's kinetic. Finally, interactions 
may appear at the synaptic level. Results of experimentation, after in 
situ injection to the cortex level, confirm that an interaction between 
the 2 enantiomers takes place at that level. A direct negative 
interaction of R-citalopram on one or several effectors that create the 
antidepressive effect seems justified. This negative interaction has 
been studied in depth. Animal models have shown that the R-enantiomer 
has no antidepressive potential and when associated with escitalopram 
prohedonic effects disappear. Escitalopram is more powerful than 
citalopram in reducing anxiety but the presence of R-citalopram reduces 
the positive effects of escitalopram. We then may conclude that 
R-citalopram antagonizes the antidepressive effects of escitalopram and 
that its presence limits the therapeutic effect and reduces the speed of 
action of citalopram. The antagonism of escitalopram by R-citalopram was 
not expected and one hypothesis is that a direct interaction between the 
2 enantiomers may occur on a particular site of the serotonin 
transporter. Results have shown that R-citalopram has a significant 
affinity only for the allosteric site of the transporter, which 
regulates the affinity of the ligand for the active site at the origin 
of serotonin reuptake inhibition. Unlike citalopram, escitalopram's 
pharmacologic action is not blocked by R-citalopram explaining its 
greater therapeutic efficacy and more rapid mode of action.

     PMID: 17675913 [PubMed - in process]>>>